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Method of preventing T cell-mediated responses by the use of the major histocompatibility complex class II analog protein (map protein) from Staphylococcus aureus

a technology of histocompatibility complex and staphylococcus aureus, which is applied in the direction of antibody medical ingredients, peptides/protein ingredients, peptides, etc., can solve the problems of dramatic alteration of their physiology

Inactive Publication Date: 2007-04-26
BROWN ERIC +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a method of using the S. aureus Map protein or its binding subdomains to immunomodulate S. aureus and protect against or treat staphylococcal infections. The invention also provides methods of using isolated Map proteins or their effective fragments to prevent T cell-mediated responses in Staphylococcal bacteria and reduce or prevent bacterial diseases. The use of the Map protein or its subdomains can help reduce T cell proliferation and achieve a significant reduction in T cell-mediated processes such as delayed-type hypersensitivity (DTH). The invention also includes suitable compositions and vaccines based on the isolated MAP protein and its effective regions and subdomains.

Problems solved by technology

Once the bacteria have successfully adhered and colonized host tissues, their physiology is dramatically altered and damaging components such as toxins and proteolytic enzymes are secreted.

Method used

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  • Method of preventing T cell-mediated responses by the use of the major histocompatibility complex class II analog protein (map protein) from Staphylococcus aureus
  • Method of preventing T cell-mediated responses by the use of the major histocompatibility complex class II analog protein (map protein) from Staphylococcus aureus
  • Method of preventing T cell-mediated responses by the use of the major histocompatibility complex class II analog protein (map protein) from Staphylococcus aureus

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[0033] Overview

[0034]Staphylococcus aureus (SA) expresses a 72-kDa protein with the capacity to bind to a variety of extracellular matrix components (ECM), suggesting that at least one role for this protein involves adherence and colonization of host tissues. Analysis of Map, however, also revealed homologies to a segment of the peptide-binding groove of the b chain of the major histocompatability class (MHC) II mammalian proteins. Map-deficient SA (Map− SA) were generated to examine Map's role in the infection process. Map−SA-infected mice presented with significantly reduced levels of arthritis, osteomylitis, and abscess formation compared to Map+SA-infected control animals. Furthermore, Map−SA-infected mice challenged with Map+SA were significantly protected against SA-induced pathology compared to mice infected and challenged with Map+SA. Native and recombinant forms of Map were tested for their ability to interfere with T cell response in vivo and in vitro. T cells or mice tre...

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Abstract

A method of immunomodulating the T cell response in Staphylococcal bacteria is provided wherein an effective amount of the Map protein from Staphylococcus aureus is administered to a host to prevent or suppress the T cell response. The present method may be utilized with either the Map protein or an effective subdomain or fragment thereof such as the Map19 protein. The present invention is advantageous in that suppression or prevention of the T cell response in a host can prevent or ameliorate a wide variety of the pathogenic conditions such as toxic shock syndrome and other diseases associated with the T cell-mediated response caused by staphylococcal infection, and is particularly useful in cases where patients have had chronic or recurrent infections from S. aureus or other staphylococcal bacteria.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a divisional application of U.S. patent application Ser. No. 10 / 041,775, filed Jan. 10, 2002, and claims the benefit of U.S. Provisional application Ser. No. 60 / 260,523, filed Jan. 10, 2001, said applications incorporated herein by reference.FIELD OF THE INVENTION [0002] The present invention relates in general to the utilization of major histocompatibility complex class II analog protein, or “Map” protein, and its biologically effective fragments and domains thereof, in therapeutic methods to combat bacterial infection and associated immunological disruption, and in particular to the use of the Map protein and effective or active fragments thereof, including the Map19 protein, in methods of suppressing or modulating T cell-mediated responses to infection from staphylococcal bacteria such as Staphylococcus aureus, so as to be useful in the treatment of and protection against S. aureus infections. BACKGROUND OF THE IN...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/02A61K38/00C07K14/31
CPCA61K38/00C07K14/31
Inventor BROWN, ERICLEE, LAWRENCEHOOK, MAGNUS
Owner BROWN ERIC
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